ObjectiveThe purpose of the present paper was to evaluate the safety and clinical efficacy of mini‐open retroperitoneal oblique lumbar interbody fusion (OLIF) for the treatment of lumbar spinal tuberculosis.MethodsA total of 115 patients who suffered from lumbar spinal tuberculosis from June 2014 to December 2017 were included in this research. A total of 59 patients underwent OLIF and percutaneous pedicle screw fixation (OLIF group) and 56 patients underwent the anterior‐only approach (anterior‐only group). All patients were followed up for at least 24 months. Operation time, blood loss, and rate of complications were used to assess the safety of these two techniques. The visual analog scale (VAS) and the Oswestry disability index (ODI) were used to evaluate the relief of neurological and functional symptoms. The erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP) were measured to investigate the activity and recurrence of spinal tuberculosis. The Cobb angle, the sagittal vertical axis of the spine (SVA), the pelvic tilt (PT), the sacral slope (SS), the pelvic incidence (PI), and postoperative Frankel classification were also used to assess the efficiency of the spine deformity correction and the recovery of long‐term neurological function.ResultsMost patients were successfully treated with OLIF and the anterior‐only technique and attained satisfactory clinical efficiency during the 24‐month follow‐up period. In the perioperative period, the mean operative time (154.68 ± 23.64 min, P < 0.001), the mean blood loss (110.57 ± 87.67 mL, P < 0.001), and the mean hospital stay (9.55 ± 3.62 days, P < 0.001) of the OLIF group were all significantly lower than in the anterior‐only group (172.49 ± 25.67 min, 458.56 ± 114.89 mL, and 14.89 ± 3.89 days, respectively). A total of 10 patients (16.95%) experienced complications in the OLIF group, including neurological injury, segmental artery and iliac vein lacerations, peritoneal injury, instrument failure, and infection of incisions; this rate of complications was lower than in the anterior‐only group (37.50%, P = 0.013). Regard to spinal deformity correction, the Cobb angle (9.42° ± 1.72°, P = 0.032), the SVA (2.23 ± 1.07 cm, P = 0.041), the PT (14.26° ± 2.37°, P = 0.037), and the SS (39.49° ± 2.17°, P = 0.042) of the OLIF group at last follow‐up were all significantly different when compared to the anterior‐only group (14.75° ± 2.13°, 3.48 ± 0.76 cm, 18.58° ± 1.45°, and 36.78° ± 1.96°, respectively). The VAS and the ODI of the OLIF group at 1 week postoperatively (3.15 ± 0.48, 21.85 ± 3.78, P = 0.032, 0.037) and at the last follow‐up (2.12 ± 0.35, 16.70 ± 5.25, P = 0.043, 0.035) were both lower than for the anterior‐only group (5.18 ± 0.56, 29.83 ± 5.42 and 3.67 ± 0.62, 20.68 ± 6.23). The Frankel classification was improved for both OLIF and anterior‐only patients; however, there were 35 cases (59.32%) classified as Frankel grade E in the OLIF group and 22 cases (39.29%, P = 0.021) in the anterior‐only groupConclusionThe OLIF surgical technique for single lumbar (L2–L5) spinal tuberculosis is less invasive, has lower complication rates, and is more efficient than the anterior‐only approach. However, the long‐term effects of this surgical technique still need to be explored.